Human skin is continually assaulted by environmental conditions such as the sun, wind, and pollution. These environmental assaults age the visible layer of skin and reduce. the ability of the skin to serve as an effective barrier layer against the environment. This weathering causes undesirable conditions that include wrinkles, age spots, roughness, scaling, flaking, uneven appearance,.and uneven coloration. In addition, the effects of natural aging also cause the skin to wrinkle.
These negative effects can be prevented, or at least ameliorated, by applying skin care cosmetics that contain skin benefit agents that increase exfoliation according to the present invention.
Human skin may be classified into two major parts: the outer layer or epidermis and an underlying layer or dermis. The dermis contains, among other things, blood vessels, nerves, collagen, elastin, and fibroblast cells, which are responsible for the biosynthesis of collagen and elastin.
The epidermis may be considered to consist of two major zones, an inner or malpighian layer, and an outer or horny layer. The inner malpighian layer, a living tissue, may be further divided into basal, spinous, and granular layers. The outer horny layer, a dead tissue, is also referred to as stratum corneum.
In the natural skin renewal process, basal cells move outward from the basal layer and pass through the spinous and granular layers to become dead cells called corneocytes, in the stratum corneum. This process of forming corneocytes is called keratinization. The stratum corneum consists of approximately 14 layers of dead cells and is the skin tissue that one feels when touching the surface of the skin.
In normal skin, it takes about 14 days for the basal cells to move from the basal layer to the end of the granular layer and to become corneocytes, and another 14 days for the corneocytes to reach the outermost layer of the stratum corneum, where they are naturally shed or exfoliated. Thus, it takes about 28 days for cells of the basal layer to move outward to the surface in the course of skin renewal.
Based on this understanding of skin behavior, two common methods are used to improve the appearance of the skin through the application of topical compositions. In the first, a composition is applied that protects the living portion of the skin from damage. In the second, a composition is applied that increases the natural exfoliation rate (cell renewal rate) of the skin, thus increasing the rate at which the outer layers of dead cells (the stratum corneum) are replaced.
One conventional method of protecting the living skin cells from oxidative damage is by applying a composition containing xcex1-Tocopherol (naturally occurring Vitamin E) to the surface of the skin. Naturally occurring Vitamin E is oil-soluble and can improve the appearance of the skin through continued use by penetrating the outer layers of the skin to protect the living skin cells from oxidative attack, such as from radicals and peroxides. Additional oil-soluble Vitamin E derivatives, including ester derivatized Vitamin E, Tocopheryl Acetate, Tocopheryl Linoleate, Tocopheryl Linoleate/Oleate, Tocopheryl Nicotinate, and Tocopherol (vitamin E alcohol), can also serve to protect living skin cells from oxidative attack. Naturally occurring Vitamin E and its oil-soluble derivatives are believed to improve the appearance of skin by reducing oxidative damage to living cells. These oil-soluble preparations are not known ;to increase exfoliation (skin cell-renewal) rate.
Unlike oil-soluble vitamin E derivatives, water soluble vitamin E derivatives are known to prevent damage to organs when administered internally. U.S. Pat. No. 6,022,867, the entire contents of which is incorporated herein by reference, except that in the event of any inconsistent disclosure or definition from the present application, the disclosure or definition herein shall prevail, describes a water-soluble Vitamin E derivative, DL-xcex1-Tocopheryl Phosphate (VEP). The derivative is prepared by reacting Vitamin E with sodium phosphate. The ""867 patent discloses how VEP can improve the health of animals when administered internally. Similarly, WO 93/15731 discloses how internally administering phosphate derivitized Vitamin E to mice can prevent liver damage. Unlike prior oil-soluble Vitamin E preparations, VEP is soluble in water.
Another conventional method to improve the appearance of the skin is to increase the natural exfoliation rate (cell renewal rate) of the outermost part of the stratum corneum, thus exposing lower layers of the stratum corneum, through the application of exfoliating acids. Unlike the previously discussed method of protecting living skin cells with oil-soluble Vitamin E and its oil-soluble. derivatives, here the exfoliating acids speed the; natural exfoliation process by acting on the layers of dead skin cells. Many exfoliating acids are known to increase the rate of natural exfoliation. Exfoliating acids include glycolic acid, lactic acid, citric acid, malic acid, tartaric acid, salicylic acid, acetic acid, pyruvic acid, poly hydroxy acids (including gluconolactone and derivatives) and the alpha and beta hydroxycarboxylic acids that have recently received an increasing amount of attention. The lower molecular weight, short chain acids, such as lactic and glycolic acid, are the exfoliating acids most widely used in cosmetics.
A significant drawback to the use of acids as exfoliating agents, including hydroxycarboxylic acids, is that they are most effective at low pH, about 4.0 or less. As disclosed in Yu, R. J., et al. xe2x80x9cBioavailability of Alpha-Hydroxy Acids in Topical Formulations,xe2x80x9d Cosmetic Dermatology, Vol. 9, No. 6 (June 1996), acidic exfoliating agents are believed to deprotonate at a pH of about 3.8, thus losing their beneficial activity at higher pH due to a lack of bioavailability. The inability of exfoliating acids to maintain their effectiveness at higher pH ranges was also demonstrated in Smith, W. P., xe2x80x9cHydroxy Acids and Skin Aging,xe2x80x9d Soap/Cosmetics/Chemical Specialties, pp. 54-58, 76 (September 1993).
Another drawback to the use of exfoliating acids is that a strong correlation exists between their ability to exfoliate (increase cell renewal rate) and the degree of skin irritation that results. This increased irritation is likely attributable to the acidity of the active agent. Therefore, for compositions relying on exfoliating acids to increase cell renewal rates, the degree of exfoliation increases with an increase in acidity and irritation. Thus, in actual use, the amount of beneficial skin exfoliation that an exfoliating acid can deliver may not be limited by the exfoliation ability of the acid, but by how often the composition can be applied to the skin without undue irritation.
As previously stated, at a pH of about 4.0 or less, exfoliating acids, which include hydroxycarboxylic acids, demonstrate a significant stimulation of cell renewal coupled with an undesirable level of skin irritation. However, as the pH of the acidic composition is increased to approach neutral (7.0), cell renewal, in addition to skin irritation, rapidly decreases. Thus, it would be beneficial to provide an exfoliating composition that increases the rate of natural skin exfoliation without the skin irritation associated with exfoliating acids. It would be most desirable to provide for enhanced skin exfoliation at a pH more closely approaching neutral to reduce skin irritation. Thee present compositions provide enhanced skin exfoliation at a higher pH and with lower irritation than conventional exfoliating acids, thus overcoming a significant disadvantage of acidic exfoliants.
In one aspect, the present invention provides a cosmetic or dermopharmaceutical composition for topical use comprising a water-soluble Vitamin E derivative and a carrier that includes water. The water-soluble Vitamin E derivative is preferably a water-soluble salt of Vitamin E and is in the water phase.
In another aspect, a water-soluble Vitamin E derivative is present in the composition in an amount effective to increase the rate of natural skin exfoliation at a pH that significantly reduces skin irritation in comparison with prior exfoliating acids. The water-soluble Vitamin E derivative enhances the rate of skin exfoliation without undue irritation.
In accordance with this aspect of the present invention, there is provided a composition including a water-soluble Vitamin E derivative present in a therapeutically effective amount in a, topically acceptable carrier for application to human skin to increase the natural rate of skin exfoliation. Preferably, the composition contains from about 0.05% to about 30% of a water-soluble Vitamin E derivative and has a pH in the range from about 4.5 to 9.
Another aspect of the present invention includes a method of increasing the rate of skin exfoliation comprising topically applying a cosmetic composition containing an amount of a water-soluble Vitamin E derivative effective to enhance the rate of skin cell exfoliation beyond the naturally occurring rate of skin cell exfoliation. In this aspect, the method includes topically applying to the skin a composition comprising a water-soluble Vitamin E derivative in an amount and for a period of time sufficient to increase the rate of natural skin exfoliation.
The present invention relates to compositions that enhance the rate of skin cell renewal or exfoliation and to a method of increasing the skin cell renewal rate. The compositions are believed to act by increasing the exfoliation or xe2x80x9creleasexe2x80x9d of dead cells, not by repairing or protecting living skin cells from damage, including oxidative damage from radicals and peroxides. Thus, the present compositions increase the rate at which dead keratinizing cells are released; they are not believed to protect living cells from damage.
In particular, the present invention relates to a composition containing a skin benefiting agent that includes a water-soluble Vitamin E derivative that stimulates cell renewal, but does not unduly irritate at the desired pH. In an especially preferred aspect, the present invention includes a composition including sodium phosphate derivatized Vitamin E (VEP). The present invention also relates to a method of increasing the rate of skin-cell exfoliation by applying a composition to the skin, wherein the composition comprises an effective amount of a water-soluble Vitamin E derivative and a carrier.
In accordance with one aspect of the present invention, a composition acceptable for topical application to the skin comprises a water-soluble Vitamin E salt and a carrier.
The water-soluble Vitamin E salts useful in the present invention include all enantiomers whether singly or in combination. With respect to the salts, preferable salts include phosphates and sulfates, with phosphate salts being presently preferred. The cation portion of the salt includes, but is not limited to alkali and alkaline earth metals such as sodium, potassium, calcium, and magnesium. The cations can be used alone or in a mixture of two or more. Sodium is a preferred cation for the salt.
Suitable water-soluble Vitamin E derivatives include, but are not limited to, Sodium Vitamin E Phosphate (VEP), Lauryl Imino Dipropionic Acid Tocopheryl Phosphate, Tocopheryl Glucoside, Tocopheryl Succinate, Tocophersolan (Tocopheryl Polyethylene Glycol 1000 Succinate), Tocophereth-5, 10, 12, 18, and 50 (polyethylene glycol (PEG) tocopheryl ethers). For the PEG vitamin E derivatives, increasing numbers represent increasing numbers of PEG molecules attached to the Vitamin E. Thus, as the number increases, so does water solubility, with Tocopereth-5 having the lowest water solubility and Tocopereth-50 having the greatest solubility in water. Preferred water-soluble Vitamin E derivatives include Sodium Vitamin E Phosphate (VEP) and Lauryl Imino Dipropionic Acid Tocopheryl Phosphate.
To prepare the compositions according to the present invention, at least one of the aforementioned water-soluble Vitamin E salts is mixed with a pharmaceutically or cosmetically acceptable carrier that includes water. Desirably, from about 0.05% to about 30% of the composition is the water-soluble Vitamin E derivative, more preferably from about 0.1% to about 15%. At present, a composition including from about 0.4% to about 5% of the water-soluble Vitamin E derivative is especially preferred. Unless stated otherwise, all percentages are given on a weight/weight basis.
Desirably, the carrier is capable of assisting in maintaining the desired pH of the composition. The pH values for the compositions of the present invention are from about 4.5 to about 9, preferably from 4.8 to 8.2, and more preferably from 5.6 to 7.9.
While the difference in the numerical value of these pH ranges is small, the difference in acidity is substantial because of the logarithmic relationship between numerical pH values and acidity. Thus, a pH of 5 is an order of magnitude less acidic than a pH of 4.
Desirably, the water-soluble Vitamin E derivative is not combined to form a composition containing exfoliating acids, squalene, or squalane. A xe2x80x9csqualanexe2x80x9d is a saturated hydrocarbon formed by reduction of squalene, an unsaturated hydrocarbon occurring. in fish and plant oils. In another aspect, the composition does not include an exfoliating acid at a concentration sufficient to provide an increase in exfoliation rate. In another aspect, the composition does not contain greater than 2% of an exfoliating acid. In yet another aspect, the composition does not contain an exfoliating acid having a bioavailability of 4% or greater, more preferably 1% or greater.
The compositions of the present invention may be formulated as a water-based solution, gel, lotion, cream, ointment, oil-in-water emulsion, water-in-oil emulsion, or other pharmaceutically acceptable form. If, however, the water-based composition contains oil, the water-soluble Vitamin E salt is substantially in the water phase.
The cosmetically acceptable carrier includes water and preferably acts as a dilutant, dispersant, or carrier for other cosmetic ingredients present in the composition, so as to facilitate their distribution when the composition is applied to the skin. Preferably, the composition includes from 5 to 98% water and more preferably from 80 to 98% water.
The compositions of the present invention may also contain various conventional cosmetic ingredients, so long as they do not detrimentally affect the desired enhancement of skin exfoliation or composition pH. Suitable cosmetic ingredients can include liquid or solid emollients, organic or inorganic sunscreens, preservatives, buffers, solvents, humectants, viscosity modifiers, alcohols, fats, oils, surfactants, fatty acids, silicone oils, moisturizers, emulsifiers, stabilizers, coloring agents and perfumes. The claimed compositions may also include propellants such as propane, isobutane, dimethyl ether, carbon dioxide, and nitrous oxide.
As used herein, xe2x80x9cemollientsxe2x80x9d refer to materials used for the prevention or relief of dryness, as well as for the protection of the skin. Wide varieties of suitable emollients as described in Sagarin, Cosmetics, Science and Technology, 2nd Edition, Vol. 1, pp. 32-43 (1972), and incorporated herein by reference, are known and may be used herein.
The compositions can .optionally include inorganic and organic sunscreens as cosmetic ingredients that provide protection from the harmful effects of excessive exposure to sunlight during use. In one aspect, preferable compositions include from 0.1 to 10% and more preferably from 1 to 5% of an organic sunscreen.